Management of Uncontrolled Asthma on Current Therapy
Before escalating therapy, you must systematically verify medication adherence, assess inhaler technique, and review environmental triggers—these are the most common causes of apparent treatment failure and must be addressed first. 1, 2
Initial Assessment (Before Any Medication Changes)
Critical first steps:
- Verify adherence through direct questioning, pharmacy refill records, or medication monitoring devices 1
- Assess inhaler technique by having the patient demonstrate their technique—improper use is a leading cause of treatment failure 1
- Review environmental exposures including allergens, irritants, occupational triggers, and viral infections 3
- Evaluate comorbidities such as gastroesophageal reflux disease, rhinosinusitis, or medication interactions (NSAIDs, beta-blockers) 3
Common pitfall: Physicians and patients frequently underestimate symptom severity—39-70% of patients report good control despite having moderate symptoms 3. Use objective measures rather than subjective patient reports.
Defining Uncontrolled Asthma
Your patient has uncontrolled asthma if they experience any of the following 3:
- Symptoms more than twice per week
- Nighttime awakenings more than twice per month
- Short-acting beta-agonist use more than twice per week (excluding exercise prophylaxis)
- Any interference with normal activities
- FEV1 or peak flow <80% predicted
- More than one exacerbation requiring systemic corticosteroids in the past year
Step-Up Treatment Algorithm
If Currently on Low-Dose ICS + Albuterol (Step 2):
Add a long-acting beta-agonist (LABA) to the ICS regimen 3. This represents stepping up to Step 3 therapy. The combination of ICS + LABA is more effective than doubling the ICS dose 2.
Critical safety warning: LABAs must never be used as monotherapy—the FDA has issued a black-box warning against LABA monotherapy due to increased risk of asthma-related death 3, 4. Always use LABA in combination with ICS, preferably in a single inhaler device 1.
Preferred approach: Use a single combination inhaler (e.g., fluticasone/salmeterol, budesonide/formoterol) rather than two separate devices, as this improves adherence and outcomes 1.
If Currently on Medium-Dose ICS-LABA (Step 3):
Increase to high-dose ICS-LABA combination 5. For example, if on Advair 250 (fluticasone/salmeterol 250/50 mcg), increase to Advair 500 (fluticasone/salmeterol 500/50 mcg) twice daily 5.
If Currently on High-Dose ICS-LABA (Step 4):
Add tiotropium (long-acting muscarinic antagonist/LAMA) to the existing ICS-LABA regimen 1. This is recommended for patients ≥12 years with moderate certainty of evidence 1.
Important caveat: Do not simply increase ICS doses beyond high-dose levels—this provides minimal clinical benefit while substantially increasing risks of systemic adverse effects including reduced bone mineral density and growth suppression 3, 5.
Alternative option: Consider adding a leukotriene modifier (montelukast or zafirlukast) to high-dose ICS-LABA, though evidence is more limited 3.
If Requiring Step 5-6 Therapy:
Refer to an asthma specialist 3, 1. At this level, consider:
- Omalizumab (anti-IgE) for patients ≥12 years with allergic asthma (elevated IgE, positive skin testing or RAST) 3
- Other biologic therapies (anti-IL5/5R, anti-IL4R) for severe persistent asthma with type 2 inflammation 5
Monitoring and Follow-Up
Reassess in 2-6 weeks after stepping up therapy 1, 5. Use validated questionnaires:
- Asthma Control Test (ACT)
- Asthma Control Questionnaire (ACQ)
- Asthma Therapy Assessment Questionnaire (ATAQ) 1
Track exacerbation frequency: More than 2 exacerbations requiring oral corticosteroids per year indicates poor control regardless of symptom scores 5.
Step down therapy after 3-6 months of good control to identify the minimum medication necessary to maintain control 3, 2.
Evidence Hierarchy
The recommendation to add LABA to ICS is supported by high-quality evidence showing an 87% relative risk reduction in exacerbations requiring systemic corticosteroids (RR 0.87,95% CI 0.76-0.99), with a number needed to treat of 62 6. LABA + ICS also demonstrates superior improvements in lung function, symptoms, rescue medication use, and quality of life compared to adding leukotriene modifiers 6.
However, there is a concerning trend toward increased serious adverse events with LABA compared to leukotriene modifiers (RR 1.33,95% CI 0.99-1.79, P=0.06), representing an absolute increase of one percentage point 6. This underscores the importance of using the lowest effective dose and considering alternatives when appropriate.
Special Considerations for Mild Asthma
For patients with mild intermittent or mild persistent asthma, as-needed combination ICS-albuterol therapy (e.g., budesonide 250 mcg + albuterol 100 mcg) is as effective as regular daily ICS and results in lower cumulative corticosteroid exposure 7, 8. This represents a paradigm shift from traditional fixed-dose daily ICS therapy 2.